Microarray analysis and RNA silencing link fra-1 to cd44 and c-met expression in mesothelioma.
Microarray analysis and RNA silencing link fra-1 to cd44 and c-met expression in mesothelioma.
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发表时间：
2003-07
期刊：
影响因子：
11.2
通讯作者：
M. Ramos-Nino;L. Scapoli;M. Martinelli;S. Land;B. Mossman
中科院分区：
文献类型：
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作者：
M. Ramos-Nino;L. Scapoli;M. Martinelli;S. Land;B. Mossman
恶性间皮瘤是一种与接触石棉有关的预后不良的癌症。石棉诱发的间皮瘤的机制尚不清楚，需要进行研究以找到诊断工具和治疗方法来提高患者的生存率。在对正常大鼠胸膜间皮瘤（RPM）细胞、暴露于青石棉的RPM细胞和大鼠间皮瘤进行寡核苷酸微阵列分析（Affyssin阵列）后，对表达改变的基因子集进行分类，包括高度上调的早期反应原癌基因fra-1。随后使用实时定量PCR证实大鼠和人类间皮瘤中fra-1的增加以及石棉暴露的RPM细胞和间皮瘤中共同的一个基因子集，其模拟fra-1的表达模式。利用RNA干扰技术，通过实时定量PCR检测fra-1基因沉默的RPM细胞中可能的fra-1调控基因的表达。结果显示cd 44和c-met的诱导与fra-1的表达有因果关系，将fra-1与间皮瘤中控制细胞运动和侵袭的基因联系起来。这些研究表明，抑制fra-1信号通路可能是恶性间皮瘤的治疗策略。
Malignant mesothelioma is a cancer with poor prognosis associated with exposures to asbestos. The mechanisms of asbestos-induced mesotheliomas are unclear, and studies are required to find diagnostic tools and therapies to improve the survival rates of patients. After oligonucleotide microarray analysis (Affymetrix array) of normal rat pleural mesothelial (RPM) cells, RPM cells exposed to crocidolite asbestos, and rat mesotheliomas, subsets of genes that changed in expression were categorized, including the highly up-regulated, early response proto-oncogene, fra-1. Increases in fra-1 in both rat and human mesotheliomas and a subset of genes common to both asbestos-exposed RPM cells and mesotheliomas that mimicked fra-1 patterns of expression were subsequently confirmed using real-time quantitative PCR. Using RNA interference technology, fra-1 gene silenced RPM cells were assayed by real-time quantitative PCR for the expression of possible fra-1-regulated genes. Results reveal that induction of cd44 and c-met is causally linked to fra-1 expression, connecting fra-1 with genes governing cell motility and invasion in mesothelioma. These studies suggest that inhibition of fra-1 signaling pathways may be a strategy for therapy of malignant mesothelioma.